tbuckley/cabot-search huggingface dataset:
IL7-receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK-inhibition
Authors: Lucien Courtois, Aurelie Cabannes-Hamy, Rathana Kim, Marine Delecourt, Antoine Pinton, Guillaume Charbonnier, Mélanie Féroul, Charlotte Smith, Giulia Tueur, Cecile Pivert, Estelle Balducci, Mathieu Simonin, Laure Hélène Angel, Salvatore Spicuglia, Nicolas Boissel, Guillaume P Andrieu, Vahid Asnafi, Philippe Rousselot, Ludovic Lhermitte
Journal: Blood (2023)

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted-therapies. Activating mutations of the IL7-receptor pathway genes (IL7Rp) play a proven leukemia-supportive role in T-ALL. JAK-inhibitors such as ruxolitinib have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK-inhibitors are still lacking. Herein, we show that IL7R (CD127) expression is more frequent (~70%) than IL7Rp-mutations in T-ALL (~30%). We compared the so-called non-expressers (no IL7R-expression/IL7Rp-mutation), expressers (IL7R-expression without IL7Rp-mutation) and mutants (IL7Rp-mutations). Integrative multi-omics analysis outlined IL7R-deregulation in virtually all T-ALL subtypes, at the epigenetic-level in non-expressers, genetic-level in mutants, and post-transcriptional level in expressers. Ex-vivo data using primary-derived xenografts support that IL7Rp is functional whenever the IL7R is expressed, regardless of the IL7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL7R-expression and IL7Rp-addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting achievement of complete remission in two patients with refractory/relapsed-T-ALL. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.
Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.1
Authors: Navneet Singh, Ishmael A. Jaiyesimi, Nofisat Ismaila, Natasha B. Leighl, Hirva Mamdani, Tanyanika Phillips, Dwight H. Owen
Journal: Journal of Clinical Oncology (2023)

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis; as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.
Viral bloodstream detection in mpox patients: An observational multicentric study
Authors: Alberto Rizzo, Davide Moschese, Benedetta Trentacapilli, Maria Vittoria Cossu, Andrea Giacomelli, Federica Salari, Micol Bianchi, Angelo Roberto Raccagni, Valeria Micheli, Andrea Gori, Emanuela Messina, Spinello Antinori, Maria Rita Gismondo, Antonella Castagna, Davide Mileto, Giuliano Rizzardini, Alessandra Lombardi, Silvia Nozza
Journal: Journal of Infection (2023)
Increased Technology Use Associated With Lower A1C in a Large Pediatric Clinical Population
Authors: G. Todd Alonso, Taylor M. Triolo, Halis Kaan Akturk, Meghan E. Pauley, Marisa Sobczak, Gregory P. Forlenza, Casey Sakamoto, Laura Pyle, Brigitte I. Frohnert
Journal: Diabetes Care (2023)

OBJECTIVE While continuous glucose monitors (CGMs), insulin pumps, and hybrid closed-loop (HCL) systems each improve glycemic control in type 1 diabetes, it is unclear how the use of these technologies impacts real-world pediatric care. RESEARCH DESIGN AND METHODS We found 1,455 patients aged &amp;lt;22 years, with type 1 diabetes duration &amp;gt;3 months, and who had data from a single center in between both 2016–2017 (n = 2,827) and 2020–2021 (n = 2,731). Patients were grouped by multiple daily injections or insulin pump, with or without an HCL system, and using a blood glucose monitor or CGM. Glycemic control was compared using linear mixed-effects models adjusting for age, diabetes duration, and race/ethnicity. RESULTS CGM use increased from 32.9 to 75.3%, and HCL use increased from 0.3 to 27.9%. Overall A1C decreased from 8.9 to 8.6% (P &amp;lt; 0.0001). CONCLUSIONS Adoption of CGM and HCL was associated with decreased A1C, suggesting promotion of these technologies may yield glycemic benefits.
Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer
Authors: Rajendra A. Badwe, Vani Parmar, Nita Nair, Shalaka Joshi, Rohini Hawaldar, Suraj Pawar, Geeta Kadayaprath, Bibhuti B. Borthakur, Subramanyeshwar Rao Thammineedi, Shashank Pandya, Satheesan Balasubramanian, Priyadarshan V. Chitale, Rakesh Neve, Caleb Harris, Anurag Srivastava, Shabina Siddique, Vaibhav J. Vanmali, Ashwini Dewade, Varsha Gaikwad, Sudeep Gupta
Journal: Journal of Clinical Oncology (2023)

Preventing metastases by using perioperative interventions has not been adequately explored. Local anesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral infiltration of local anesthesia on disease-free survival (DFS).Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumor size, and center. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively.Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P = .017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P = .019). The impact of LA was similar in subgroups defined by menopausal status, tumor size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection.Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228).[Media: see text].
Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine
Authors: Ye Che, Alexey V. Gribenko, Xi Song, Luke D. Handke, Kari S. Efferen, Kristin Tompkins, Srinivas Kodali, Lorna Nunez, A. Krishna Prasad, Lynn M. Phelan, Mark Ammirati, Xiaodi Yu, Joshua A. Lees, Wei Chen, Lyndsey Martinez, Vidia Roopchand, Seungil Han, Xiayang Qiu, John P. DeVincenzo, Kathrin U. Jansen, Philip R. Dormitzer, Kena A. Swanson
Journal: Science Translational Medicine (2023)

Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum-neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization.
Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.1
Authors: Navneet Singh, Ishmael A. Jaiyesimi, Nofisat Ismaila, Natasha B. Leighl, Hirva Mamdani, Tanyanika Phillips, Dwight H. Owen
Journal: Journal of Clinical Oncology (2023)

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis; as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.
Social prescribing is no remedy for health inequalities
Authors: Andrew Moscrop
Journal: BMJ (2023)

The Times recently suggested social prescribing may be "a waste of NHS money." 1 Other sources more accurately reported the "absence of evidence" to support social prescribing. 2Media attention followed publication of a systematic review showing "little or no impact" on mental health or health related quality of life, and little evidence to support other purported outcomes of social prescribing. 38
Chronic thromboembolic pulmonary hypertension – the challenging approach of a young patient with distal disease
Authors: M. Martinho, R. Calé, F. Ferreira, S. Alegria, A. Santos, A.C. Vieira, D. Repolho, S. Vitorino, C. Saraiva, H. Pereira
Journal: Pulmonology (2023)
Availability and Accessibility of Live Nonreplicating Smallpox/Mpox Vaccine
Authors: Peter A. Kahn, Xiaohan Ying, Michael Virata, Patrick Magahis, Sunnie Li, Walter S. Mathis
Journal: JAMA Network Open (2023)

This cross-sectional study compares the availability and accessibility of mpox vaccine sites with the number of reported cases and allocated vaccines.
The DNA Damage Response and Inflammation in Cancer
Authors: Vanessa Klapp, Beatriz Álvarez-Abril, Giuseppe Leuzzi, Guido Kroemer, Alberto Ciccia, Lorenzo Galluzzi
Journal: Cancer Discovery (2023)

Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting the demise of cells with unrepairable DNA lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR sig-naling can also favor tumor progression and resistance to therapy. Indeed, DDR signaling in cancer cells has been consistently linked to the inhibition of tumor-targeting immune responses. Here, we discuss the complex interactions between the DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy. Accumulating preclinical and clinical evidence indicates that DDR is intimately connected to the emission of immunomodulatory signals by normal and malignant cells, as part of a cell-extrinsic program to preserve organismal homeostasis. DDR-driven inflammation, however, can have diametrically opposed effects on tumor-targeting immunity. Understanding the links between the DDR and inflammation in normal and malignant cells may unlock novel immunotherapeutic paradigms to treat cancer.
A new clinical severity score for the management of acute small bowel obstruction in predicting bowel ischemia: a cohort study
Authors: Charles-Henri Wassmer, Rebecca Revol, Isabelle Uhe, Mickaël Chevallay, Christian Toso, Pascal Gervaz, Philippe Morel, Pierre-Alexandre Poletti, Alexandra Platon, Frederic Ris, Frank Schwenter, Thomas Perneger, Raphael P.H. Meier
Journal: International Journal of Surgery (2023)

Small bowel obstruction (SBO) is a common hospital admission diagnosis. Identification of patients who will require a surgical resection because of a nonviable small bowel remains a challenge. Through a prospective cohort study, the authors aimed to validate risk factors and scores for intestinal resection, and to develop a practical clinical score designed to guide surgical versus conservative management.All patients admitted for an acute SBO between 2004 and 2016 in the center were included. Patients were divided in three categories depending on the management: conservative, surgical with bowel resection, and surgical without bowel resection. The outcome variable was small bowel necrosis. Logistic regression models were used to identify the best predictors.Seven hundred and thirteen patients were included in this study, 492 in the development cohort and 221 in the validation cohort. Sixty-seven percent had surgery, of which 21% had small bowel resection. Thirty-three percent were treated conservatively. Eight variables were identified with a strong association with small bowel resection: age 70 years of age and above, first episode of SBO, no bowel movement for greater than or equal to 3 days, abdominal guarding, C-reactive protein greater than or equal to 50, and three abdominal computer tomography scanner signs: small bowel transition point, lack of small bowel contrast enhancement, and the presence of greater than 500 ml of intra-abdominal fluid. Sensitivity and specificity of this score were 65 and 88%, respectively, and the area under the curve was 0.84 (95% CI: 0.80-0.89).The authors developed and validated a practical clinical severity score designed to tailor management of patients presenting with an SBO.
Treatment for acute uncomplicated diverticulitis without antibiotherapy: systematic review and meta-analysis of randomized clinical trials
Authors: Alba Correa Bonito, Carlos Cerdán Santacruz, Marcello Di Martino, Lara Blanco Terés, Álvaro Gancedo Quintana, Elena Martín-Pérez, Sebastiano Biondo, Javier García Septiem
Journal: International Journal of Surgery (2023)

Use of antibiotics in selected cases of acute uncomplicated diverticulitis (AUD) has recently been questioned.The aim of this study is to examine the safety and efficacy of treatment regimens without antibiotics compared with that of traditional treatments with antibiotics in selected patients with AUD.PubMed, Medline, Embase, Web of Science, and the Cochrane Library.A systematic review was performed according to PRISMA and AMSTAR guidelines by searching through Medline, Embase, Web of Science, and the Cochrane Library for randomized clinical trials (RCTs) published before December 2022. The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis.RCTs on treating AUD without antibiotics published in English before December 2022 were included.Treatments without antibiotics were compared with treatments with antibiotics.The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis.The search yielded 1163 studies. Four RCTs with 1809 patients were included in the review. Among these patients, 50.1% were treated conservatively without antibiotics. The meta-analysis showed no significant differences between nonantibiotic and antibiotic treatment groups with respect to rates of readmission [odds ratio (OR)=1.39; 95% CI: 0.93-2.06; P =0.11; I2 =0%], change in strategy (OR=1.03; 95% CI: 0.52-2,02; P =0.94; I2 =44%), emergency surgery (OR=0.43; 95% CI: 0.12-1.53; P =0.19; I2 =0%), worsening (OR=0.91; 95% CI: 0.48-1.73; P =0.78; I2 =0%), and persistent diverticulitis (OR=1.54; 95% CI: 0.63-3.26; P =0.26; I2 =0%).Heterogeneity and a limited number of RCTs.Treatment for AUD without antibiotic therapy is safe and effective in selected patients. Further RTCs should confirm the present findings.
Indocyanine green fluorescence imaging to localize insulinoma and provide three-dimensional demarcation for laparoscopic enucleation: a retrospective single-arm cohort study
Authors: Haisu Tao, Xiaojun Zeng, Wenjun Lin, Zhuangxiong Wang, Jinyu Lin, Jiang Li, Yinling Qian, Jian Yang, Chihua Fang
Journal: International Journal of Surgery (2023)

Background: Indocyanine green (ICG) fluorescence imaging is a new technology that can improve the real-time location of tumor edges and small nodules during surgery. However, no study has investigated its application in laparoscopic insulinoma enucleation. This study aimed to evaluate the feasibility and accuracy of this method for intraoperative localization of insulinomas and margin assessment during laparoscopic insulinoma enucleation. Materials and Methods: Eight patients who underwent laparoscopic insulinoma enucleation from October 2016 to June 2022 were enrolled. Two methods of ICG administration, ICG dynamic perfusion and three-dimensional (3D) demarcation staining, were utilized in the laparoscopic insulinoma enucleation. Tumor-to-background ratio (TBR) and histopathologic analysis were used to evaluate the feasibility and accuracy of these novel navigation methods in laparoscopic insulinoma enucleation. Results: All eight enrolled patients underwent both ICG dynamic perfusion and 3D demarcation staining. ICG dynamic perfusion images were available for six of them, among which five tumors could be recognized by TBR (largest TBR in each case 4.42±2.76), while the other could be distinguished by the disordered blood vessels in the tumor area. Seven out of eight specimens had successful 3D demarcation staining (TBR 7.62±2.62). All wound bed margins had negative frozen sections and final histopathologic diagnoses. Conclusions: ICG dynamic perfusion may be helpful in observing the abnormal vascular perfusion of tumors, providing similar functionality to intraoperative real-time angiography. ICG injection under the tumor pseudocapsule may be a useful method for acquiring real-time, 3D demarcation for the resection of insulinoma.
Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis
Authors: Emily J. Schepers, Kathryn Glaser, Harrison M. Zwolshen, Stephen J. Hartman, Alexander J. Bondoc
Journal: Cancer Research (2023)

Abstract Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma (HCC). GPC3 undergoes extensive posttranslational modification (PTM) including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the PTM of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism. We propose that the function of GPC3 in normal development can vary with extensive PTM and that dysregulation of these processes leads to disease. Defining the regulatory impact of these modifications can provide a deeper understanding of the role of GPC3 in oncogenesis, epithelial–mesenchymal transition, and drug development. Through review of current literature, this article provides a unique perspective on the role of GPC3 in liver cancer, focusing on potential regulatory mechanisms of PTM on GPC3 function at the molecular, cellular, and disease level.
A commentary on ‘Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: Systematic review and meta-analysis of propensity-score matched studies’ [Int J Surg 105 (2022) 106821]
Authors: Jia Luo, Xiaohong Luo, Jing Tian, Benjian Gao, Bo Li
Journal: International Journal of Surgery (2023)

aDepartment of Oncology and Hematology, People's Hospital of Leshan, Leshan, 614000, Sichuan Province, China bDepartment of General Surgery (Hepatopancreatobiliary surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China cAcademician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author. Address: Department of Oncology and Hematology, People's Hospital of Leshan, No. 238, Baita Street, Shizhong District, Leshan, 614000, Sichuan Province, China. Tel: +86 15892925098; E-mail address: [email protected] (X. Luo). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/